1. Field of the Invention
The present invention relates to the field of ophthalmology. More particularly, the invention relates to the treatment of glaucoma and associated elevations of intraocular pressure, and to the treatment of ocular hypertension associated with other diseases or conditions. The invention is directed to providing topical, ophthalmic, pharmaceutical compositions which include, as principal active ingredients, combinations of one or more alpha-2 agonists, such as clonidine derivatives (e.g., para-amino clonidine) and one or more beta-blockers (e.g., betaxolol).
2. Discussion of Related Art
The underlying causes of glaucoma are not fully understood. The symptomatology of this disease includes elevated pressure levels within the eye. These pressure elevations may be caused by either over production of fluid within the eye, or inadequate outflow of fluid from the eye. The intraocular fluid is referred to as "aqueous humor." The internal pressure of the eye associated with the amount of fluid inside the eye is referred to as "intraocular pressure" or "IOP." Although the causes of glaucoma and associated elevations of intraocular pressure are not fully understood, the prognosis of untreated or inadequately treated glaucoma is known to include very serious ocular manifestations, namely blindness or significant loss of vision. Thus, there is a continuing need for therapies which control the elevated intraocular pressure associated with glaucoma.
A significant number of glaucoma patients are required to administer more than one drug in order to achieve therapeutic control of their intraocular pressure. In other words, a single drug does not provide adequate control of intraocular pressure in these patients. The drugs currently utilized in the treatment of glaucoma include miotics (e.g., pilocarpine, carbachol, and acetylcholinesterase inhibitors), sympathomimetics (e.g., epinephrine and dipivalylepinephrine), beta-blockers (e.g., betaxolol, levobunolol and timolol), alpha-2 agonists (e.g., para-amino clonidine) and carbonic anhydrase inhibitors (e.g., acetazolamide, methazolamide and ethoxzolamide). Miotics and sympathomimetics are believed to lower intraocular pressure by increasing the outflow of aqueous humor, while beta-blockers, alpha-2 agonists and carbonic anhydrase inhibitors are believed to lower intraocular pressure by decreasing the formation of aqueous humor. All five types of drugs have potential side effects. Miotics, such as pilocarpine, can cause blurring of vision and other visual side effects which may either decrease patient compliance or require termination of miotic drug therapy. Carbonic anhydrase inhibitors can also cause serious side effects which affect patient compliance and/or necessitate withdrawal of the drug therapy. At least one beta-blocker, timolol, has increasingly become associated with serious pulmonary side effects attributable to its effect on beta-2 receptors in pulmonary tissue. In addition to these side effects, a therapy regimen which includes the use of two or more pharmaceutical compositions containing drugs selected from two or more of the above-cited classes requires the patient to apply the compositions to the affected eye(s) in separate, spaced dosages, several times per day. Patient compliance with such complicated dosage regimens can be very poor, particularly in elderly patients. Since the majority of glaucoma patients are elderly, this patient compliance problem is significant.
In light of the foregoing circumstances, it is clear that a need exists for new, more potent antiglaucoma compositions which avoid or reduce the above-cited side effects and enhance patient compliance. The present invention is directed to the provision of such compositions.